tbuckley/cabot-search huggingface dataset:
MASALA Study Probes Why People With South Asian Ancestry Have Increased Cardiovascular Disease Risks
Authors: Jennifer Abbasi
Journal: JAMA (2022)

This Medical News article is an interview with Alka Kanaya, MD, and Namratha Kandula, MD, MPH, principal investigators on the Mediators of Atherosclerosis in South Asians Living in America (MASALA) prospective cohort study.
Conductive and Semiconductive Nanocomposite‐Based Hydrogels for Cardiac Tissue Engineering
Authors: Sania Ghobadi Alamdari, Abbas Alibakhshi, Miguel de la Guardia, Behzad Baradaran, Reza Mohammadzadeh, Mohammad Amini, Prashant Kesharwani, Ahad Mokhtarzadeh, Fatemeh Oroojalian, Amirhossein Sahebkar
Journal: Advanced Healthcare Materials (2022)

Cardiovascular disease is the leading cause of death worldwide and the most common cause is myocardial infarction. Therefore, appropriate approaches should be used to repair damaged heart tissue. Recently, cardiac tissue engineering approaches have been extensively studied. Since the creation of the nature of cardiovascular tissue engineering, many advances have been made in cellular and scaffolding technologies. Due to the hydrated and porous structures of the hydrogel, they are used as a support matrix to deliver cells to the infarct tissue. In heart tissue regeneration, bioactive and biodegradable hydrogels are required by simulating native tissue microenvironments to support myocardial wall stress in addition to preserving cells. Recently, the use of nanostructured hydrogels has increased the use of nanocomposite hydrogels and has revolutionized the field of cardiac tissue engineering. Therefore, to overcome the limitation of the use of hydrogels due to their mechanical fragility, various nanoparticles of polymers, metal, and carbon are used in tissue engineering and create a new opportunity to provide hydrogels with excellent properties. Here, the types of synthetic and natural polymer hydrogels, nanocarbon-based hydrogels, and other nanoparticle-based materials used for cardiac tissue engineering with emphasis on conductive nanostructured hydrogels are briefly introduced.
Telomere Length and Development of Systemic Lupus Erythematosus: A Mendelian Randomization Study
Authors: Xu‐Fan Wang, Wen‐Jing Xu, Fei‐Fei Wang, Rui Leng, Xiao‐Ke Yang, Hua‐Zhi Ling, Yin‐Guang Fan, Jin‐Hui Tao, Zong‐Wen Shuai, Li Zhang, Dong‐Qing Ye, Rui‐Xue Leng
Journal: Arthritis & Rheumatology (2022)

Objective Previous observational studies demonstrated that a subset of patients with systemic lupus erythematosus (SLE) have markedly short telomere length in leukocytes. This study was undertaken to test whether leukocyte telomere length is causally associated with risk of SLE. Methods A 2‐sample Mendelian randomization (MR) analysis was conducted to estimate causality of telomere length on SLE in European populations. A replication 2‐sample MR study using Asian genetic data was also conducted. A reverse MR analysis was then performed to test the effects of SLE on telomere length. The autoantibodies targeting telomere‐associated protein (telomeric repeat–binding factor 1 [TERF1] autoantibodies) were detected in patients with SLE, healthy controls, and patients with rheumatoid arthritis. Results The results of the inverse variance–weighted method (odds ratio [OR] 2.96 [95% confidence interval (95% CI) 1.58–5.55], P &lt; 0.001) showed strong evidence for a causal relationship between longer telomere length and risk of SLE in people with European ancestry. The outcomes of MR‐Egger regression analysis (OR 29.46 [95% CI 3.02–287.60], P = 0.033) and MR pleiotropy residual sum and outlier analysis (OR 3.62 [95% CI 2.03–6.46], P = 0.002) also showed that longer telomere length was significantly associated with increased risk of SLE in a European population. Sensitivity analyses using different methods and summary data sets showed that the results were still broadly consistent. A replication MR study using Asian genetic data yielded similar findings. However, the reverse MR analysis showed that genetically predicted SLE was not causally associated with telomere length. In addition, we found that TERF1 autoantibodies were present in 2 of 40 SLE patients (5.0%). Conclusion In contrast with previous observational studies, MR analyses show that longer telomere length is significantly associated with increased risk of SLE.
Molluscum Contagiosum Therapeutics—New Options May Be Around the Corner
Authors: Vikash S. Oza
Journal: JAMA Dermatology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
STS pathogenic variants in a Dutch patient cohort clinically suspected for X-linked ichthyosis show genetic heterogeneity
Authors: Ivo F. Nagtzaam, Frank S. van Leersum, Laurie C.M. Kouwenberg, Marinus J. Blok, Maaike Vreeburg, Peter M. Steijlen, Antoni Gostyński, Michel van Geel
Journal: British Journal of Dermatology (2022)

Abstract
Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study
Authors: Chloe R. McDonald, Aleksandra Leligdowicz, Andrea L. Conroy, Andrea M. Weckman, Melissa Richard-Greenblatt, Michelle Ngai, Clara Erice, Kathleen Zhong, Sophie Namasopo, Robert O. Opoka, Michael T. Hawkes, Kevin C. Kain
Journal: PLoS Medicine (2022)

Background Despite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death. Methods and findings We conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia. Circulating plasma markers of immune (IL-6, IL-8, CXCL-10/IP-10, CHI3L1, sTNFR1, and sTREM-1) and endothelial (sVCAM-1, sICAM-1, Angpt-1, Angpt-2, and sFlt-1) activation measured at hospital presentation were compared to lactate, respiratory rate, oxygen saturation, procalcitonin (PCT), and C-reactive protein (CRP) with a primary outcome of predicting 48-hour mortality. Of 805 children with IMCI pneumonia, 616 had severe pneumonia. Compared to 10 other immune and endothelial activation markers, sTREM-1 levels at presentation had the best predictive accuracy in identifying 48-hour mortality for children with pneumonia (AUROC 0.885, 95% CI 0.841 to 0.928; p = 0.03 to p &lt; 0.001) and severe pneumonia (AUROC 0.870, 95% CI 0.824 to 0.916; p = 0.04 to p &lt; 0.001). sTREM-1 was more strongly associated with 48-hour mortality than lactate (AUROC 0.745, 95% CI 0.664 to 0.826; p &lt; 0.001), respiratory rate (AUROC 0.615, 95% CI 0.528 to 0.702; p &lt; 0.001), oxygen saturation (AUROC 0.685, 95% CI 0.594 to 0.776; p = 0.002), PCT (AUROC 0.650, 95% CI 0.566 to 0.734; p &lt; 0.001), and CRP (AUROC 0.562, 95% CI 0.472 to 0.653; p &lt; 0.001) in cases of pneumonia and severe pneumonia. The main limitation of this study was the unavailability of radiographic imaging. Conclusions In this cohort of Ugandan children, sTREM-1 measured at hospital presentation was a significantly better indicator of 48-hour mortality risk than other common approaches to risk stratify children with pneumonia. Measuring sTREM-1 at clinical presentation may improve the early triage, management, and outcome of children with pneumonia at risk of death. Trial registration The trial was registered at clinicaltrial.gov ( NCT 04726826 ).
Alteration of the gut microbiota’s composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters
Authors: Valentin Sencio, Nicolas Benech, Cyril Robil, Lucie Deruyter, Séverine Heumel, Arnaud Machelart, Thierry Sulpice, Antonin Lamazière, Corinne Grangette, François Briand, Harry Sokol, François Trottein
Journal: Gut Microbes (2022)

Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota's composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota's composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota's metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.
Heterozygous variants in the integrin subunit beta 4 gene (ITGB4) cause autosomal dominant nail dystrophy
Authors: Kiril Malovitski, Odile Meijers, Eran Cohen-Barak, James Bergman, Noam Adir, Moshe Giladi, Stavit Shalev, Ofer Sarig, Janice Schwartz, Holly Evans, Eli Sprecher, Liat Samuelov
Journal: British Journal of Dermatology (2022)

Abstract
The Critical Importance of Timing of Source Control in Patients With Community-Acquired Sepsis
Authors: Pamela A. Lipsett
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Safety of heterologous primary and booster schedules with ChAdOx1-S and BNT162b2 or mRNA-1273 vaccines: nationwide cohort study
Authors: Niklas Worm Andersson, Emilia Myrup Thiesson, Mona Vestergaard Laursen, Stine Hasling Mogensen, Jesper Kjær, Anders Hviid
Journal: BMJ (2022)

To assess the risk of adverse events associated with heterologous primary (two dose) and booster (three dose) vaccine schedules for covid-19 with Oxford-AstraZeneca's ChAdOx1-S priming followed by mRNA vaccines (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) as compared with homologous mRNA vaccine schedules for covid-19.Nationwide cohort study.Denmark, 1 January 2021 to 26 March 2022.Adults aged 18-65 years who received a heterologous vaccine schedule of priming with ChAdOx1-S and one or two mRNA booster doses (with either the BNT162b2 or mRNA-1273 vaccine) were compared with adults who received a homologous BNT162b2 or mRNA-1273 vaccine schedule (ie, two dose v two dose, and three dose v three dose schedule).The incidence of hospital contacts for a range of adverse cardiovascular and haemostatic events within 28 days after the second or third vaccine dose, comparing heterologous versus homologous vaccine schedules. Secondary outcomes included additional prioritised adverse events of special interest. Poisson regression was used to estimate incidence rate ratios with adjustment for selected covariates.Individuals who had had a heterologous primary vaccine (n=137 495) or a homologous vaccine (n=2 688 142) were identified, in addition to those who had had a heterologous booster (n=129 770) or a homologous booster (n=2 197 213). Adjusted incidence rate ratios of adverse cardiovascular and haemostatic events within 28 days for the heterologous primary and booster vaccine schedules in comparison with the homologous mRNA vaccine schedules were 1.22 (95% confidence interval 0.79 to 1.91) and 1.00 (0.58 to 1.72) for ischaemic cardiac events, 0.74 (0.40 to 1.34) and 0.72 (0.37 to 1.42) for cerebrovascular events, 1.12 (0.13 to 9.58) and 4.74 (0.94 to 24.01) for arterial thromboembolisms, 0.79 (0.45 to 1.38) and 1.09 (0.60 to 1.98) for venous thromboembolisms, 0.84 (0.18 to 3.96) and 1.04 (0.60 to 4.55) for myocarditis or pericarditis, 0.97 (0.45 to 2.10) and 0.89 (0.21 to 3.77) for thrombocytopenia and coagulative disorders, and 1.39 (1.01 to 1.91) and 1.02 (0.70 to 1.47) for other bleeding events, respectively. No associations with any of the outcomes were found when restricting to serious adverse events defined as stay in hospital for more than 24 h.Heterologous primary and booster covid-19 vaccine schedules of ChAdOx1-S priming and mRNA booster doses as both second and third doses were not associated with increased risk of serious adverse events compared with homologous mRNA vaccine schedules. These results are reassuring but given the rarity of some of the adverse events, associations cannot be excluded.
Antibody variable region engineering for improving cancer immunotherapy
Authors: Hantao Lou, Xuetao Cao
Journal: Cancer Communications (2022)

Abstract The efficacy and specificity of conventional monoclonal antibody (mAb) drugs in the clinic require further improvement. Currently, the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention. Variable region‐retaining antibody fragments, such as antigen‐binding fragment (Fab), single‐chain variable fragment (scFv), bispecific antibody, and bi/trispecific cell engagers, are engineered with humanization, multivalent antibody construction, affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody‐based therapy potency, efficacy and specificity. In this review, we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.
Optimizing the Design and Analysis of Future AKI Trials
Authors: Matthieu Legrand, Sean M. Bagshaw, Jay L. Koyner, Ivonne H. Schulman, Michael R. Mathis, Juliane Bernholz, Steven Coca, Martin Gallagher, Stéphane Gaudry, Kathleen D. Liu, Ravindra L. Mehta, Romain Pirracchio, Abigail Ryan, Dominik Steubl, Norman Stockbridge, Fredrik Erlandsson, Alparslan Turan, F. Perry Wilson, Alexander Zarbock, Michael P. Bokoch, Jonathan D. Casey, Patrick Rossignol, Michael O. Harhay
Journal: Journal of the American Society of Nephrology (2022)

AKI is a complex clinical syndrome associated with an increased risk of morbidity and mortality, particularly in critically ill and perioperative patient populations. Most AKI clinical trials have been inconclusive, failing to detect clinically important treatment effects at predetermined statistical thresholds. Heterogeneity in the pathobiology, etiology, presentation, and clinical course of AKI remains a key challenge in successfully testing new approaches for AKI prevention and treatment. This article, derived from the “AKI” session of the “Kidney Disease Clinical Trialists” virtual workshop held in October 2021, reviews barriers to and strategies for improving the design and implementation of clinical trials in patients with, or at risk of, developing AKI. The novel approaches to trial design included in this review span adaptive trial designs that increase the knowledge gained from each trial participant; pragmatic trial designs that allow for the efficient enrollment of sufficiently large numbers of patients to detect small, but clinically significant, treatment effects; and platform trial designs that use one trial infrastructure to answer multiple clinical questions simultaneously. This review also covers novel approaches to clinical trial analysis, such as Bayesian analysis and assessing heterogeneity in the response to therapies among trial participants. We also propose a road map and actionable recommendations to facilitate the adoption of the reviewed approaches. We hope that the resulting road map will help guide future clinical trial planning, maximize learning from AKI trials, and reduce the risk of missing important signals of benefit (or harm) from trial interventions.
Complex Interaction of Lithium With Kidney and Bone Health
Authors: Jonathan Houle, Lorne Schweitzer, Kyle T. Greenway
Journal: JAMA Psychiatry (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Efficacy and Safety of Topical Nitric Oxide−Releasing Berdazimer Gel in Patients With Molluscum Contagiosum
Authors: John C. Browning, Carolyn Enloe, Martina Cartwright, Adelaide Hebert, Amy S. Paller, David Hebert, Elaine Kearney Kowalewski, Tomoko Maeda-Chubachi
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Molluscum contagiosum (MC) is a highly contagious skin condition. Lesions may persist for months to years, and no US Food and Drug Administration–approved medications are currently available in the US. <h3>Objective</h3> To assess the efficacy and safety of berdazimer gel, 10.3%, a novel topical nitric oxide–releasing medication, in the treatment of MC. <h3>Design, Setting, and Participants</h3> This was a multicenter, vehicle-controlled, double-blind, phase 3 randomized clinical trial (B-SIMPLE4) conducted in 55 clinics (mostly dermatology and pediatric) in the US from September 1, 2020, to July 21, 2021. Eligible participants were 6 months or older and had from 3 to 70 raised MC lesions. Patients with sexually transmitted MC or with MC only in the periocular area were excluded. <h3>Interventions</h3> Patients were randomized to treatment with berdazimer gel, 10.3%, or vehicle gel, applied as a thin layer to all lesions once daily for 12 weeks. <h3>Main Outcomes and Measures</h3> The primary efficacy end point was complete clearance of all MC lesions at week 12. Safety and tolerability measures included adverse event frequency and severity, and assessment of local skin reactions and scarring. Data analyses were performed from August 31, 2021, to September 14, 2021. <h3>Results</h3> A total of 891 participants were randomized, 444 to berdazimer, 10.3% (mean [range] age, 6.6 [0.9-47.5] years; 228 [51.4%] male; 387 [87.2%] White individuals), and 447 to vehicle (mean [range] age, 6.5 [1.3-49.0] years; 234 [52.3%] female; 382 [85.5%] White individuals). In the intention-to-treat population, 88.5% (393 patients) in the berdazimer group and 88.8% (397 patients) in the vehicle group had a lesion count performed at week 12. At week 12, 32.4% (144 patients) in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% (88 patients) in the vehicle group (absolute difference, 12.7%; odds ratio, 2.0; 95% CI, 1.5-2.8;<i>P</i> &lt; .001) with 14.4% (64 patients) of the berdazimer group discontinuing treatment because of MC clearance compared with 8.9% (40 patients) of the vehicle group. Adverse event rates were low. The most common adverse events were application-site pain and erythema, mostly mild in severity. Adverse events leading to discontinuation affected 4.1% (18 patients) of the berdazimer group and 0.7% (3 patients) of the vehicle group. The most common local skin reaction was mild to moderate erythema. <h3>Conclusions and Relevance</h3> Use of berdazimer gel, 10.3%, for MC appears to demonstrate favorable efficacy and safety with low adverse event rates. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT04535531